Isocyanates are widely used in the plastics industry for preparation of polyurethanes. Adverse effects of various isocyanates such as asthma and contact dermatitis are well-recognized occupational hazards. This proposal is designed to investigate the immunological basis of these isocyanate reactions. Immunological effects of aromatc diisocyanate (TDI toluene diisocyanate) and aliphatic diisocyanate (HDI hexamethylene diisocyante) will be studied in both animals and humans. Various isocyanate-protein conjugates prepared under controlled laboratory conditions will be characterized by determining precise adduct-carrier ratios. Inducton of homocytotropic and precipitating antibodies by isocyanate-protein conjugates will be investigated in guinea pigs and mice. Effects of chronic inhalation of isocyanate compounds and protein conjugates will be studied in guinea pigs. Investigation of humoral and delayed hypersensitivity will be conducted in TDI- and HDI-sensitive workers. Bronchial provocation tests to isocyanate vapours and aerosol mists of protein conjugates will also be performed in sensitized workers.